Qiu Yuan-Ye, Tang Li-Qin, Wei Wei
Institute of Clinical Pharmacology, Anhui Medical University, 81#Mei-shan Road, Hefei 230032, Anhui, People's Republic of China; Department of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, 17# Lu-jiang Road, Hefei 230001, Anhui, People's Republic of China.
Department of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, 17# Lu-jiang Road, Hefei 230001, Anhui, People's Republic of China.
Mol Cell Endocrinol. 2017 Mar 5;443:89-105. doi: 10.1016/j.mce.2017.01.009. Epub 2017 Jan 10.
In this study, we explored the effect of berberine treatment on the AGEs-RAGE pathway in a rat model of diabetic nephropathy, and we investigated the mechanism by which key factors caused kidney injury and the effects of berberine. In vivo, berberine improved fasting blood glucose, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney. Western blotting and immunohistochemistry revealed significant increases in the levels of AGEs, RAGE, P-PKC-β and TGF-β1 in injured kidneys, and these levels were markedly decreased by treatment with berberine. In vitro, berberine inhibited mesangial cell proliferation. Cells treated with berberine showed reduced levels of AGEs, accompanied by decreased RAGE, p-PKC and TGF-β1 levels soon afterwards. Berberine exhibited renoprotective effects in diabetic nephropathy rats, and the molecular mechanism was associated with changes in the levels and regulation of the AGEs-RAGE-PKC-β-TGF-β1 signaling pathway.
在本研究中，我们在糖尿病肾病大鼠模型中探究了黄连素治疗对晚期糖基化终末产物-晚期糖基化终末产物受体（AGEs-RAGE）通路的影响，并研究了关键因素导致肾损伤的机制以及黄连素的作用。在体内，黄连素改善了空腹血糖、体重、大多数生化和肾功能参数以及糖尿病肾脏的组织病理学变化。蛋白质免疫印迹法和免疫组织化学显示，损伤肾脏中AGEs、RAGE、磷酸化蛋白激酶C-β（P-PKC-β）和转化生长因子-β1（TGF-β1）水平显著升高，而黄连素治疗使这些水平明显降低。在体外，黄连素抑制系膜细胞增殖。用黄连素处理的细胞AGEs水平降低，随后RAGE、磷酸化蛋白激酶C（p-PKC）和TGF-β1水平也随之下降。黄连素对糖尿病肾病大鼠具有肾脏保护作用，其分子机制与AGEs-RAGE-PKC-β-TGF-β1信号通路水平及调控的变化有关。
